Amiodarone: Pharmacology and Adverse Effects

Amiodarone is an iodinated benzofuran derivative, structurally similar to thyroid hormones, and contains about 37% of organic iodine. It is a widely used drug for the treatment of tachyarrhythmias and, to a lesser extent, ischemic heart disease. The primary pharmacological actions of amiodarone are class III antiarrhythmic properties, which involve the prolongation of cardiac action potential time. It also possesses class I activity, antisympathetic properties (class II), and negative chronotropic effects (class IV).

Amiodarone has a slow and variable absorption rate, with a bioavailability of about 40%. The onset of action may take several days to a few weeks, and the steady-state plasma levels range from 1.07 to 1.19 µg/mL but are up to 20 times more concentrated in the thyroid. The bioavailability may be influenced by age, liver disease, and interactions with other drugs or substances that inhibit or induce cytochrome (CYP) 450.

Amiodarone is also known to affect the thyroid. It releases 50- to 100-fold excess iodine daily, which can cause changes in thyroid function tests, such as an increase in serum T4 and rT3, and a decrease in serum T3 concentrations, mainly related to the inhibition of 5'-deiodinase activity. In 14-18% of amiodarone-treated patients, there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities.

Amiodarone therapy is associated with numerous significant adverse effects, and there is also a risk of adverse interactions with other medications. Therefore, it is crucial for prescribing clinicians to seek consultation with a cardiologist and for patients to undergo baseline testing for thyroid, pulmonary, and ophthalmologic toxicity. Regular follow-up testing is also necessary.

Amiodarone is associated with adverse effects such as corneal microdeposits, which occur in at least 90% of patients taking amiodarone, although only about 10% of these patients will develop actual visual symptoms. It can also cause cardiac toxicity, which can be attributed to its therapeutic mechanism, and may be associated with an increased risk of drug-induced Torsades de Pointes (TdP) within the first 48 hours of IV administration.

In conclusion, amiodarone is a widely used antiarrhythmic drug with a unique pharmacological profile and potential adverse effects on the thyroid and other organs. It is essential for prescribing clinicians to understand these effects and to provide appropriate monitoring and management for patients receiving amiodarone therapy.